DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 4-12, 14, 15 and 17-19 are pending in this application, Claims 14, 15 and 17 are acknowledged as withdrawn, Claims 4-12, 18 and 19 were examined on their merits.
The objection to the Specification due to improper use of Trademarks has been withdrawn due to the Applicant’s amendments to the Specification filed 05/26/2026.
The rejection(s) of Claims 4-10 under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, has been withdrawn due to the Applicant’s amendments to the claims filed 05/26/2026.
The rejection of Claim 4 under 35 U.S.C. § 102(a)(1) as being anticipated by Wada et al. (2000), cited in the IDS, has been withdrawn due to the Applicant’s amendments to the claims filed 05/26/2026.
The rejection of Claims 4 and 6-10 under 35 U.S.C. § 102(a)(1) as being anticipated by Patel et al. (05/31/2021), cited in the IDS, has been withdrawn due to the Applicant’s amendments to the claims filed 05/26/2026.
The rejection of Claim(s) 4-10 under 35 U.S.C. § 103 as being unpatentable over
Patel et al. (05/31/2021), cited in the IDS, and further in view of Zhang et al. (2020) and Jahnen-Dechent et al. (US 2014/0377874 A1), has been withdrawn due to the Applicant’s amendments to the claims filed 05/26/2026.
Claim Interpretation
Claim 6 has been construed under product-by-process consistent with the MPEP
at 2113, I., wherein the product “(TEBV) comprising a tubular structure formed from a plurality of stacked ring-shaped vascular grafts, each ring-shaped vascular graft comprising: self-assembled vascular cells, integrated with an acellular tissue matrix derived from decellularized biological tissue, wherein the acellular tissue matrix comprises collagen and a fibrin hydrogel; and an endothelial cell monolayer, lining a luminal surface of the tubular structure" is made by the process; "comprising: (i) co-culturing a group of vascular cells with the acellular tissue matrix and the fibrin hydrogel in a container comprising a central supporting post, wherein the vascular cells self-assemble into a ring-shaped cellular structure around the supporting post and integrate with the acellular tissue matrix and fibrin hydrogel; (ii) stacking a plurality of the ring-shaped cellular structures to form the tubular structure;
(iii) seeding endothelial cells into the tubular structure; (iv) adding the oxLDL to the fibrin hydrogel during step (i) or to the tubular structure following step (iii); (v) introducing macrophages into a lumen of the vessel; and (vi) introducing CPPs into the vessel wall to induce smooth muscle cell secretion of calcium into the acellular tissue matrix".
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7 and 8 are newly rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 7 refers to, “the cells” but it is unclear what cells are being referred to as Claim 6 from which it depends recites “vascular cells” and “macrophages” and Claim 4 from which both Claims 6 and 7 depend recites “vascular cells” and “endothelial cells”. Claim 8 is rejected as being dependent upon rejected Claim 7 and for failing to resolve the indefiniteness of Claim 7.
Claim 9 recites the limitation "the group of cells". There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 4, 6-10 and 18 are newly rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Patel et al. (05/31/2021), cited in the IDS, as necessitated by Applicant’s amendments to the claims filed 05/26/2026.
Patel et al. teaches an in vitro tissue-engineered blood vessel (TEBV) comprising a tubular structure formed of multiple stacked ring formation plates, each ring comprising: self-assembled vascular cells (human dermal fibroblasts) integrated with an acellular tissue matrix (ALLODERM™) comprising collagen (Pg. 9, Figs. 4g and i) and a fibrin hydrogel (Pg. 2, Lines 29-34 and Pg. 3, Lines 1-19 and Pg. 5, Fig. 1);
an endothelial (HUVEC) cell monolayer lining the luminal surface of the tubular structure (Pg. 12, Lines 3-6 and Pg. 13, Fig. 11) and reading on Claims 4, 6 and 7;
wherein the hydrogel comprises ascorbic acid and TGF-β (Pg. 2, Lines 55-61),
and reading on Claim 8;
and a 6 mm diameter cylindrical supporting post contacting the cells, hydrogel and acellular tissue matrix (Pg. 5, Fig. 1 and Pg. 2, Lines 47-53), reading on Claims 9 and 10.
With regard to the limitations of Claim 6, the Examiner notes that the “product” of the prior art “in vitro tissue-engineered blood vessel (TEBV)” is identical to the product of the prior art as set forth above, even if produced by a different process. Therefore, burden is shifted to Applicant to establish a non-obvious difference. See the MPEP at 2113, I. and II.
With regard to Claim 18, Patel et al. teaches forming a tubular structure by stacking ring-shaped vascular grafts around the 6mm diameter cylindrical supporting post wherein each ring-shaped vascular grafts will have an inner diameter of about 6mm and an outer diameter of about 13mm (Pg. 11, Lines 7-8 and Pg. 13, Fig. 10 and Pg. 5, Fig. 1).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 4, 6-10 and 18 are newly rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Patel et al. (05/31/2021), cited in the IDS, as applied to Claims 4, 6-10 and 18 above, and further in view of Zhang et al. (2020) and Jahnen-Dechent et al. (US 2014/0377874 A1), both of record, as necessitated by Applicant’s amendments to the claims filed 05/26/2026.
The teachings of Patel et al. were discussed above.
Patel et al. did not teach a method wherein the TEBV further comprises oxidized LDL within the acellular tissue matrix, macrophages that have engulfed the oxidized LDL to form foam cells and calcified protein particles, as required by Claim 5.
Zhang et al. teaches an in vitro TEBV model of early stage atherosclerosis which can identify the role of drugs on specific vascular functions that cannot be assessed in vivo (Pg. 1, Abstract) by application of modified LDL which are engulfed by macrophages to form foam cells (Pg. 2, Column 1, Lines 11-14 and Pg. 3, Fig. 1a[ii]) and wherein LDL can be modified by oxidation, acetylation and enzymatic modification (Pg. 5, Lines 6-7).
Jahnen-Dechent et al. teaches that that the most common form of calcification is atherosclerosis (Pg. 1, Paragraph [0006]), that cardiovascular calcification is the formation of one or more plaques localized in one or more blood vessels which may be characterized by the incorporation of low-density lipoprotein (LDL) and/or white blood cells, especially macrophages that have taken up oxidized low-density lipoprotein (LDL) which may lead to atherosclerosis (Pg. 2, Paragraph [0026]) and wherein calcification is any deposition and/or precipitation of poorly soluble or insoluble calcium salts and/or the formation of calciprotein particles (CPPs) in vivo and in vitro (Pg. 2, Paragraph [0022]).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the in vitro TEBV model of Patel et al. by application of (oxidized) LDL within the acellular tissue matrix which induce macrophages to engulf the oxLDL and form foam cells as in the early stage model of atherosclerosis of Zhang et al. because this would provide an in vitro atherosclerosis model using simulated blood vessels. Those of ordinary skill in the art would have been motivated to make this modification in order to assess drug effects which cannot be tested in vivo. There would have been a reasonable expectation of success in making this modification because both Patel and Zhang are drawn to the same field of endeavor, that is, in vitro TEBV models.
It would have been further obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the in vitro TEBV model of atherosclerosis of Patel et al. and Zhang et al. with the inclusion of CPPs, as taught by Jahnen-Dechent et al. because this would provide a further parameter in the pathology of atherosclerosis, the calcification (plaque formation) in the in vitro blood vessel model of atherosclerosis. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare an in vitro model of atherosclerosis which more closely resembles the in vivo disease. There would have been a reasonable expectation of success in making this modification because both Patel and Zhang are drawn to the same field of endeavor, that is, in vitro TEBV models, Zhang teaches an in vitro TEBV model of atherosclerosis and Jahnen-Dechent et al. teaches that CPP mediate blood vessel calcification commonly found in atherosclerosis.
Claims 4-10, 18 and 19 are newly rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Patel et al. (05/31/2021), cited in the IDS, in view of Zhang et al. (2020) and Jahnen-Dechent et al. (US 2014/0377874 A1), both of record, as applied to Claims 4-10 and 18 above, and further in view of Dgany et al. (WO 99/34724), as necessitated by Applicant’s amendments to the claims filed 05/26/2026.
The teachings of Patel et al., Zhang et al. and Jahnen-Dechent et al. were discussed above.
None of the above references taught wherein the in vitro model exhibits an elastic modulus and a stiffness greater than a comparable TEBV lacking the CPPs, wherein the increased elastic modulus and stiffness are indicative of a calcified late stage disease state, as required by Claim 19.
Dgany et al. teaches that hemodynamic characteristics of blood vessels change with aging and/or disease states such as hypertension and atherosclerosis, such as large arteries dilating and stiffening and having a greater elastic modulus (Pg. 13, Lines 24-31).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the in vitro TEBV model of atherosclerosis comprising CPPs of Patel et al., Zhang et al. and Jahnen-Dechent et al. would exhibit an elastic modulus and a stiffness greater than a comparable TEBV lacking the CPPs, because Jahnen-Dechent et al. teaches that that the most common form of calcification is atherosclerosis, and that calcification is characterized by CPP formation. Dgany et al. teaches that a disease state such as atherosclerosis is characterized by blood vessels having increased stiffness and greater elastic modulus. Thus, the ordinary artisan would have reasonably expected that an in vitro TEBV model of late-stage atherosclerosis would have characteristically greater stiffness and elastic modulus than a non-atherosclerotic in vitro TEBV model due to the lack of calcification.
Those of ordinary skill in the art would have been motivated to make this modification in order to prepare an in vivo model of in vivo atherosclerosis There would have been a reasonable expectation of success in making this modification because Patel is drawn to an in vitro TEBV models, Zhang teaches an in vitro TEBV model of atherosclerosis, Jahnen-Dechent et al. teaches that CPP mediate blood vessel calcification commonly found in atherosclerosis and Dgany et al. teaches that atherosclerosis in blood vessels is characterized by stiffness and increased elastic modulus.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653
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